DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation.

Abstract

BACKGROUND:

DJ-1 is an antioxidant protein known to regulate mast cell-mediated allergic response, but its role in airway eosinophilic interactions and allergic inflammation is not known.

OBJECTIVE:

The aim of this study was to investigate the role of DJ-1 in airway eosinophilic inflammation in vitro and in vivo.

METHODS:

Ovalbumin-induced airway allergic inflammation was established in mice. ELISA was adopted to analyze DJ-1 and cytokine levels in mouse bronchoalveolar lavage fluid. Transcriptional profiling of mouse lung tissues was conducted by single-cell RNA-sequencing technology. The role of DJ-1 in the differentiation of airway progenitor cells into goblet cells was examined by organoid cultures, immunofluorescence staining, quantitative PCR, and cell transplantation in normal, DJ-1 knockout (KO), or conditional DJ-1 KO mice.

RESULTS:

This study observed that DJ-1 was increased in the lung tissues of ovalbumin-sensitized and challenged mice. DJ-1 KO mice exhibited reduced airway eosinophil infiltration and goblet cell differentiation. Mechanistically, we discovered that eosinophil-club cell interactions are reduced in the absence of DJ-1. Organoid cultures indicated that eosinophils impair the proliferative potential of club cells. Intratracheal transplantation of DJ-1-deficient eosinophils suppresses airway goblet cell differentiation. Loss of DJ-1 inhibits the metabolism of arachidonic acid into cysteinyl leukotrienes in eosinophils while these secreted metabolites promote airway goblet cell fate in organoid cultures and in vivo.

CONCLUSIONS:

DJ-1-mediated interactions between airway epithelial progenitor cells and immune cells are essential in controlling airway goblet cell metaplasia and eosinophilia. Blockade of the DJ-1 pathway is protective against airway allergic inflammation.

• Authors: Kuan Li, Qiuyang Zhang, Li Li, Shuangyan Li, Qing Yue, Xue Li, Yu Li, Jianhai Wang, Sisi Wang, Zengqiang Yuan, Huaiyong Chen
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 150 Issue 5 Pg. 1178-1193.e13 (11 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 35724763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Ovalbumin

Topics

• Mice
• Animals
• Eosinophils
• Ovalbumin
• Inflammation
• Bronchoalveolar Lavage Fluid
• Lung
• Mice, Knockout
• Eosinophilia
• Cell Communication
• Stem Cells
• Mice, Inbred BALB C